tbuckley/cabot-search huggingface dataset:
The relationship between interstitial lung abnormalities, mortality, and multimorbidity: a cohort study
Authors: Jason Leigh Sanders, Gisli Axelsson, Rachel Putman, Aravind Menon, Josée Dupuis, Hanfei Xu, Shuai Wang, Joanne Murabito, Ramachandran Vasan, Tetsuro Araki, Mizuki Nishino, George R Washko, Hiroto Hatabu, George O'Connor, Gunnar Gudmundsson, Vilmundur Gudnason, Gary M Hunninghake
Journal: Thorax (2022)

Background Interstitial lung abnormalities (ILAs) are associated with increased mortality. It is unclear whether multimorbidity accounts for the mortality association or how strongly ILA is associated with mortality relative to other common age-associated diseases. We determined the association of ILA with all-cause mortality adjusted for multimorbidity, compared mortality associated with ILA and prevalent cardiovascular disease (CVD), diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease and cancer and also determined the association between ILA and these diseases. Methods We measured ILA (none, indeterminant, definite) using blinded reads of CT images, prevalent chronic diseases and potential confounders in two observational cohorts, the Framingham Heart Study (FHS) (n=2449) and Age, Gene/Environment Susceptibility - Reykjavik Study (AGES-Reykjavik) (n=5180). We determined associations with mortality using Cox proportional hazards models and between ILA and diseases with multinomial logistic regression. Results Over a median (IQR) follow-up of 8.8 (1.4) years in FHS and 12.0 (7.7) years in AGES-Reykjavik, in adjusted models, ILAs were significantly associated with increased mortality (HR, 95% CI 1.95, 1.23 to 3.08, p=0.0042, in FHS; HR 1.60, 1.41 to 1.82, p&lt;0.0001, in AGES-Reykjavik) adjusted for multimorbidity. In both cohorts, the association of ILA with mortality was of similar magnitude to the association of most other diseases. In adjusted models, ILAs were associated only with prevalent kidney disease (OR, 95% CI 1.90, 1.01 to 3.57, p=0.0452) in FHS and with prevalent CVD (OR 1.42, 1.12 to 1.81, p=0.0040) in AGES-Reykjavik. Conclusions ILAs were associated with mortality adjusted for multimorbidity and were similarly associated with increased mortality compared with several common chronic diseases. ILAs were not consistently associated with the prevalence of these diseases themselves.
Regulation of Erythropoiesis by the Hypoxia-Inducible Factor Pathway: Effects of Genetic and Pharmacological Perturbations
Authors: Gregg L. Semenza
Journal: Annual Review of Medicine (2022)

Red blood cells transport O2 from the lungs to body tissues. Hypoxia stimulates kidney cells to secrete erythropoietin (EPO), which increases red cell mass. Hypoxia-inducible factors (HIFs) mediate EPO gene transcriptional activation. HIF-α subunits are subject to O2-dependent prolyl hydroxylation and then bound by the von Hippel-Lindau protein (VHL), which triggers their ubiquitination and proteasomal degradation. Mutations in the genes encoding EPO, EPO receptor, HIF-2α, prolyl hydroxylase domain protein 2 (PHD2), or VHL cause familial erythrocytosis. In addition to O2, α-ketoglutarate is a substrate for PHD2, and analogs of α-ketoglutarate inhibit hydroxylase activity. In phase III clinical trials evaluating the treatment of anemia in chronic kidney disease, HIF prolyl hydroxylase inhibitors were as efficacious as darbepoetin alfa in stimulating erythropoiesis. However, safety concerns have arisen that are focused on thromboembolism, which is also a phenotypic manifestation of VHL or HIF-2α mutation, suggesting that these events are on-target effects of HIF prolyl hydroxylase inhibitors.
Oxaliplatin (3 months <i>v</i> 6 months) With 6 Months of Fluoropyrimidine as Adjuvant Therapy in Patients With Stage II/III Colon Cancer: KCSG CO09-07
Authors: Seung Tae Kim, Sun Young Kim, Jeeyun Lee, Seong Hyeon Yun, Hee Cheol Kim, Woo Yong Lee, Tae Won Kim, Yong Sang Hong, Seok-Byung Lim, Ji Yeon Baek, Jae Hwan Oh, Joong Bae Ahn, Sang Joon Shin, Sae-Won Han, Seong Geun Kim, Seok Yun Kang, Sun Jin Sym, Dae Young Zang, Yeul Hong Kim, In Sil Choi, Jung Hun Kang, Min-Ji Kim, Young Suk Park
Journal: Journal of Clinical Oncology (2022)

PURPOSE The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified. PATIENTS AND METHODS This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25. RESULTS In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% v 58.3%; P &lt; .0001). The 3-year DFS rates were 83.7% and 84.7% in the 6-month and 3-month arms, respectively, with an HR of 0.953 (95% CI, 0.769 to 1.180; test for noninferiority, P = .0065) within the noninferiority margin. Among patients with stage III CRC treated by capecitabine plus oxaliplatin, the 3-year DFS of the 3-month arm was noninferior as compared with that of the 6-month arm with an HR of 0.713 (95% CI, 0.530 to 0.959; P = .0009). However, among patients with high-risk stage II and stage III CRC treated by infusional fluorouracil, leucovorin, and oxaliplatin, the noninferiority of the 3-month arm compared with the 6-month arm was not proven. CONCLUSION This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481 ).
First complex maxillofacial reconstruction with free flaps in the Gaza Strip, occupied Palestinian territory: case series from an area under conflict
Authors: Wafaa AlZaanin, Anas Ismail, Hala Shoman, Rami Al Juaidi, Aghyad Al Mobaid, Tariq Kuhail, Laurent Ganry, Quentin Qassemyar
Journal: The Lancet (2022)
Effectiveness of influenza vaccination in preventing influenza in primary care, Navarre, Spain, 2021/22
Authors: Iván Martínez-Baz, Itziar Casado, Ana Miqueleiz, Ana Navascués, Francisco Pozo, Camino Trobajo-Sanmartín, Esther Albéniz, Fernando Elía, Cristina Burgui, Miguel Fernández-Huerta, Carmen Ezpeleta, Jesús Castilla
Journal: Eurosurveillance (2022)

Compared with individuals unvaccinated in the current and three previous influenza seasons, in 2021/22, influenza vaccine effectiveness at primary care level was 37% (95% CI: 16 to 52) for current season vaccination, regardless of previous doses, and 35% (95% CI: −3 to 45) for only previous seasons vaccination. Against influenza A(H3N2), estimates were 39% (95% CI: 16 to 55) and 24% (95% CI: −8 to 47) suggesting moderate effectiveness of current season vaccination and possible remaining effect of prior vaccinations.
Reduction of Cardiac Fibrosis by Interference With YAP-Dependent Transactivation
Authors: Gloria Garoffolo, Manuel Casaburo, Francesco Amadeo, Massimo Salvi, Giacomo Bernava, Luca Piacentini, Isotta Chimenti, Germana Zaccagnini, Gesmi Milcovich, Estella Zuccolo, Marco Agrifoglio, Sara Ragazzini, Otgon Baasansuren, Claudia Cozzolino, Mattia Chiesa, Silvia Ferrari, Dario Carbonaro, Rosaria Santoro, Martina Manzoni, Loredana Casalis, Angela Raucci, Filippo Molinari, Lorenzo Menicanti, Francesca Pagano, Toshiro Ohashi, Fabio Martelli, Diana Massai, Gualtiero I. Colombo, Elisa Messina, Umberto Morbiducci, Maurizio Pesce
Journal: Circulation Research (2022)

Background: Conversion of cardiac stromal cells into myofibroblasts is typically associated with hypoxia conditions, metabolic insults, and/or inflammation, all of which are predisposing factors to cardiac fibrosis and heart failure. We hypothesized that this conversion could be also mediated by response of these cells to mechanical cues through activation of the Hippo transcriptional pathway. The objective of the present study was to assess the role of cellular/nuclear straining forces acting in myofibroblast differentiation of cardiac stromal cells under the control of YAP (yes-associated protein) transcription factor and to validate this finding using a pharmacological agent that interferes with the interactions of the YAP/TAZ (transcriptional coactivator with PDZ-binding motif) complex with their cognate transcription factors TEADs (TEA domain transcription factors), under high-strain and profibrotic stimulation. Methods: We employed high content imaging, 2-dimensional/3-dimensional culture, atomic force microscopy mapping, and molecular methods to prove the role of cell/nuclear straining in YAP-dependent fibrotic programming in a mouse model of ischemia-dependent cardiac fibrosis and in human-derived primitive cardiac stromal cells. We also tested treatment of cells with Verteporfin, a drug known to prevent the association of the YAP/TAZ complex with their cognate transcription factors TEADs. Results: Our experiments suggested that pharmacologically targeting the YAP-dependent pathway overrides the profibrotic activation of cardiac stromal cells by mechanical cues in vitro, and that this occurs even in the presence of profibrotic signaling mediated by TGF-β1 (transforming growth factor beta-1). In vivo administration of Verteporfin in mice with permanent cardiac ischemia reduced significantly fibrosis and morphometric remodeling but did not improve cardiac performance. Conclusions: Our study indicates that preventing molecular translation of mechanical cues in cardiac stromal cells reduces the impact of cardiac maladaptive remodeling with a positive effect on fibrosis.
Exercise testing in heart failure with preserved ejection fraction: an appraisal through diagnosis, pathophysiology and therapy – A clinical consensus statement of the Heart Failure Association and European Association of Preventive Cardiology of the European Society of Cardiology
Authors: Marco Guazzi, Matthias Wilhelm, Martin Halle, Emeline Van Craenenbroeck, Hareld Kemps, Rudolph A. de Boer, Andrew J.S. Coats, Lars Lund, Donna Mancini, Barry Borlaug, Gerasimos Filippatos, Burkert Pieske
Journal: European Journal of Heart Failure (2022)

Patients with heart failure with preserved ejection fraction (HFpEF) universally complain of exercise intolerance and dyspnoea as key clinical correlates. Cardiac as well as extracardiac components play a role for the limited exercise capacity, including an impaired cardiac and peripheral vascular reserve, a limitation in mechanical ventilation and/or gas exchange with reduced pulmonary vascular reserve, skeletal muscle dysfunction and iron deficiency/anaemia. Although most of these components can be differentiated and quantified through gas exchange analysis by cardiopulmonary exercise testing (CPET), the information provided by objective measures of exercise performance has not been systematically considered in the recent algorithms/scores for HFpEF diagnosis, by neither European nor US groups. The current clinical consensus statement by the Heart Failure Association (HFA) and European Association of Preventive Cardiology (EAPC) of the European Society of Cardiology (ESC) aims at outlining the role of exercise testing and its pathophysiological, clinical and prognostic insights, addressing the implications of a thorough functional evaluation from the diagnostic algorithm to the pathophysiology and treatment perspectives of HFpEF. Along with these goals, we provide a specific analysis of the evidence that CPET is the standard for assessing, quantifying, and differentiating the origin of dyspnoea and exercise impairment and even more so when combined with echocardiography and/or invasive haemodynamic evaluation. This will lead to improved quality of diagnosis when applying the proposed scores and may also help to implement the progressive characterization of the specific HFpEF phenotypes, a critical step toward the delivery of phenotype‐specific treatments.
No Association Between Amygdala Responses to Negative Faces and Depressive Symptoms: Cross-Sectional Data from 28,638 Individuals in the UK Biobank Cohort
Authors: Sandra Tamm, Catherine J. Harmer, Julian Schiel, Florian Holub, Martin K. Rutter, Kai Spiegelhalder, Simon D. Kyle
Journal: American Journal of Psychiatry (2022)
A novel AI device for real-time optical characterization of colorectal polyps
Authors: Carlo Biffi, Pietro Salvagnini, Nhan Ngo Dinh, Cesare Hassan, Prateek Sharma, Giulio Antonelli, Halim Awadie, Sebastian Bernhofer, Sabela Carballal, Mário Dinis-Ribeiro, Agnès Fernández-Clotet, Glòria Fernández Esparrach, Ian Gralnek, Yuta Higasa, Taku Hirabayashi, Tatsuki Hirai, Mineo Iwatate, Miki Kawano, Markus Mader, Andreas Maieron, Sebastian Mattes, Tastuya Nakai, Ingrid Ordas, Raquel Ortigão, Oswaldo Ortiz Zúñiga, Maria Pellisé, Cláudia Pinto, Florian Riedl, Ariadna Sánchez, Emanuel Steiner, Yukari Tanaka, Andrea Cherubini
Journal: npj Digital Medicine (2022)

Accurate in-vivo optical characterization of colorectal polyps is key to select the optimal treatment regimen during colonoscopy. However, reported accuracies vary widely among endoscopists. We developed a novel intelligent medical device able to seamlessly operate in real-time using conventional white light (WL) endoscopy video stream without virtual chromoendoscopy (blue light, BL). In this work, we evaluated the standalone performance of this computer-aided diagnosis device (CADx) on a prospectively acquired dataset of unaltered colonoscopy videos. An international group of endoscopists performed optical characterization of each polyp acquired in a prospective study, blinded to both histology and CADx result, by means of an online platform enabling careful video assessment. Colorectal polyps were categorized by reviewers, subdivided into 10 experts and 11 non-experts endoscopists, and by the CADx as either "adenoma" or "non-adenoma". A total of 513 polyps from 165 patients were assessed. CADx accuracy in WL was found comparable to the accuracy of expert endoscopists (CADxWL/Exp; OR 1.211 [0.766-1.915]) using histopathology as the reference standard. Moreover, CADx accuracy in WL was found superior to the accuracy of non-expert endoscopists (CADxWL/NonExp; OR 1.875 [1.191-2.953]), and CADx accuracy in BL was found comparable to it (CADxBL/CADxWL; OR 0.886 [0.612-1.282]). The proposed intelligent device shows the potential to support non-expert endoscopists in systematically reaching the performances of expert endoscopists in optical characterization.
Wheeze in the time of COVID-19: overcoming obstacles to an unusual diagnosis
Authors: Mhairi Barclay, Silviu Buderi, Andrew Bush, Mat Daniel, Simon Jordan, Alexandra Rice, Nigel Ruggins, Thomas Semple, Alan Robert Smyth
Journal: Thorax (2022)

This case is an example of a rare cause of a common clinical presentation (persistent lobar collapse with wheeze). We describe patient management from primary care through to a national thoracic referral centre. We highlight the importance of objective testing to support an asthma diagnosis and the need to consider alternative or additional diagnoses if a patient does not respond to treatment or the clinical course is unexpected. We highlight the importance of follow-up X-ray to determine whether atelectasis has resolved, which was significantly delayed in this case due to COVID-19 restrictions. Though rare, an endobronchial tumour should be considered if atelectasis persists and when planning endoscopy for a presumed foreign body, especially if the clinical history and patient factors make a foreign body less likely. Greater awareness of this as a differential may expedite diagnoses for patients in future. We show how virtual, multicentre, multidisciplinary meetings can aid rapid diagnosis, surgical planning and coordination of follow-up across centres.
Bookend: precise transcript reconstruction with end-guided assembly
Authors: Michael A Schon, Stefan Lutzmayer, Falko Hofmann, Michael D Nodine
Journal: Genome biology (2022)

We developed Bookend, a package for transcript assembly that incorporates data from different RNA-seq techniques, with a focus on identifying and utilizing RNA 5' and 3' ends. We demonstrate that correct identification of transcript start and end sites is essential for precise full-length transcript assembly. Utilization of end-labeled reads present in full-length single-cell RNA-seq datasets dramatically improves the precision of transcript assembly in single cells. Finally, we show that hybrid assembly across short-read, long-read, and end-capture RNA-seq datasets from Arabidopsis thaliana, as well as meta-assembly of RNA-seq from single mouse embryonic stem cells, can produce reference-quality end-to-end transcript annotations.
Tape strips capture atopic dermatitis‐related changes in nonlesional skin throughout maturation
Authors: Yael Renert‐Yuval, Ana B. Pavel, Swaroop Bose, Pedro J. Gómez‐Arias, Stephanie M. Rangel, Yeriel D. Estrada, Amy S. Paller, Emma Guttman‐Yassky
Journal: Allergy (2022)

Table S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Enoxaparin for primary thromboprophylaxis in symptomatic outpatients with COVID-19 (OVID): a randomised, open-label, parallel-group, multicentre, phase 3 trial
Authors: Stefano Barco, Davide Voci, Ulrike Held, Tim Sebastian, Roland Bingisser, Giuseppe Colucci, Daniel Duerschmied, André Frenk, Bernhard Gerber, Andrea Götschi, Stavros V Konstantinides, François Mach, Helia Robert-Ebadi, Thomas Rosemann, Noemi R Simon, Hervé Spechbach, David Spirk, Stefan Stortecky, Lukas Vaisnora, Marc Righini, Nils Kucher, Stefano Barco, Davide Voci, Ulrike Held, Tim Sebastian, Roland Bingisser, Giuseppe Colucci, Daniel Duerschmied, André Frenk, Bernhard Gerber, Andrea Götschi, Stavros V Konstantinides, François Mach, Helia Robert-Ebadi, Thomas Rosemann, Noemi R Simon, Hervé Spechbach, David Spirk, Stefan Stortecky, Lukas Vaisnora, Marc Righini, Nils Kucher, Stéphanie Roth Zetzsche, Rebecca Spescha, Claudia Leeger, Yulia Butscheid, Eliane Probst, Evy Micieli, Gabor Forgo, Fabian Johner, Alexandru Grigorean, Georgios Vatsakis, Dagmar Keller Lang, Silvana Rampini Speck, Barbara Hasse, Marco Rueegg, Isabelle Arnold, Christian Nickel, Jeannette Busch, Marc Blondon, Frédéric Glauser, Micol G Cittone, Chiara Kessler, Diona Gjermeni, Christoph B Olivier, Nadine Gauchel, Paul Biever, Lukas Hobohm, Dorothea Becker, Marc Schindewolf, Arnaud Kuenzi, Silvia Ulrich
Journal: The Lancet Haematology (2022)
NCOA4-Mediated Ferritinophagy Is a Pancreatic Cancer Dependency via Maintenance of Iron Bioavailability for Iron–Sulfur Cluster Proteins
Authors: Naiara Santana-Codina, Maria Quiles del Rey, Kevin S. Kapner, Huan Zhang, Ajami Gikandi, Callum Malcolm, Clara Poupault, Miljan Kuljanin, Kristen M. John, Douglas E. Biancur, Brandon Chen, Nupur K. Das, Kristen E. Lowder, Connor J. Hennessey, Wesley Huang, Annan Yang, Yatrik M. Shah, Jonathan A. Nowak, Andrew J. Aguirre, Joseph D. Mancias
Journal: Cancer Discovery (2022)

Pancreatic ductal adenocarcinomas (PDAC) depend on autophagy for survival; however, the metabolic substrates that autophagy provides to drive PDAC progression are unclear. Ferritin, the cellular iron storage complex, is targeted for lysosomal degradation (ferritinophagy) by the selective autophagy adaptor NCOA4, resulting in release of iron for cellular utilization. Using patient-derived and murine models of PDAC, we demonstrate that ferritinophagy is upregulated in PDAC to sustain iron availability, thereby promoting tumor progression. Quantitative proteomics reveals that ferritinophagy fuels iron-sulfur cluster protein synthesis to support mitochondrial homeostasis. Targeting NCOA4 leads to tumor growth delay and prolonged survival but with the development of compensatory iron acquisition pathways. Finally, enhanced ferritinophagy accelerates PDAC tumorigenesis, and an elevated ferritinophagy expression signature predicts for poor prognosis in patients with PDAC. Together, our data reveal that the maintenance of iron homeostasis is a critical function of PDAC autophagy, and we define NCOA4-mediated ferritinophagy as a therapeutic target in PDAC. Autophagy and iron metabolism are metabolic dependencies in PDAC. However, targeted therapies for these pathways are lacking. We identify NCOA4-mediated selective autophagy of ferritin ("ferritinophagy") as upregulated in PDAC. Ferritinophagy supports PDAC iron metabolism and thereby tumor progression and represents a new therapeutic target in PDAC. See related commentary by Jain and Amaravadi, p. 2023. See related article by Ravichandran et al., p. 2198. This article is highlighted in the In This Issue feature, p. 2007.
Conserved meningeal lymphatic drainage circuits in mice and humans
Authors: Laurent Jacob, Jose de Brito Neto, Stephanie Lenck, Celine Corcy, Farhat Benbelkacem, Luiz Henrique Geraldo, Yunling Xu, Jean-Mickael Thomas, Marie-Renee El Kamouh, Myriam Spajer, Marie-Claude Potier, Stephane Haik, Michel Kalamarides, Bruno Stankoff, Stephane Lehericy, Anne Eichmann, Jean-Leon Thomas
Journal: The Journal of Experimental Medicine (2022)

Meningeal lymphatic vessels (MLVs) were identified in the dorsal and caudobasal regions of the dura mater, where they ensure waste product elimination and immune surveillance of brain tissues. Whether MLVs exist in the anterior part of the murine and human skull and how they connect with the glymphatic system and extracranial lymphatics remained unclear. Here, we used light-sheet fluorescence microscopy (LSFM) imaging of mouse whole-head preparations after OVA-A555 tracer injection into the cerebrospinal fluid (CSF) and performed real-time vessel-wall (VW) magnetic resonance imaging (VW-MRI) after systemic injection of gadobutrol in patients with neurological pathologies. We observed a conserved three-dimensional anatomy of MLVs in mice and humans that aligned with dural venous sinuses but not with nasal CSF outflow, and we discovered an extended anterior MLV network around the cavernous sinus, with exit routes through the foramina of emissary veins. VW-MRI may provide a diagnostic tool for patients with CSF drainage defects and neurological diseases.
Impact of vaccination on the symptoms of hospitalised patients with SARS-CoV-2 Delta variant (B.1.617.1) infection
Authors: Olivier Epaulard, Sophie Abgrall, Maeva Lefebvre, Jean-François Faucher, Jocelyn Michon, Emilia Frentiu, Sophie Blanchi, Cécile Janssen, Gabrielle Charbonnier, Audrey Fresse, Simon Laurent, Lena Sandjakian, Pierre Casez, Aba Mahamat, Guillaume Beraud
Journal: Clinical Microbiology and Infection (2022)